Rao J Srinivasa, Smith Micholas Dean, Cruz Luis
Department of Physics, Drexel University , 3141 Chestnut Street, Philadelphia, Pennsylvania, 19104, United States.
J Phys Chem B. 2014 Apr 3;118(13):3517-23. doi: 10.1021/jp411122h. Epub 2014 Mar 24.
Understanding protein folding and stability in in vivo confined environments is a challenging problem from both experimental and computational points of views. Despite recent insights, an appreciation and complete understanding of how the solvent influences the structure and stability of proteins under complex confined environments is still lacking. Here, using all-atom molecular dynamics simulations in explicit solvent, we report the effects of confinement on the lifetime of a metastable β-hairpin structure in the Aβ(21-30) decapeptide. Our results show that the values of these lifetimes depend on the nature of the confining surface, where smooth and rough hydrophobic confining walls have solvent-mediated stabilizing and destabilizing effects, respectively. The source of the destabilization found inside atomically rough confining walls lies in surface-peptide interactions that break the β-hairpin in this peptide, whereas smooth confining walls stabilize it by forming well-ordered layers of water that keep the decapeptide solvated in the inner part of the pore and away from the surface. In addition, we show that the size of the confining pore can tune the value of the lifetimes where pore sizes comparable to the size of the decapeptide have the largest effects.
从实验和计算的角度来看，理解体内受限环境中的蛋白质折叠和稳定性是一个具有挑战性的问题。尽管最近有了一些见解，但对于在复杂受限环境下溶剂如何影响蛋白质的结构和稳定性，仍缺乏充分的认识和全面的理解。在这里，我们使用显式溶剂中的全原子分子动力学模拟，报告了受限环境对Aβ(21 - 30)十肽中亚稳态β-发夹结构寿命的影响。我们的结果表明，这些寿命值取决于受限表面的性质，其中光滑和粗糙的疏水受限壁分别具有溶剂介导的稳定和不稳定作用。在原子粗糙的受限壁内发现的不稳定源在于表面-肽相互作用，这种相互作用会破坏该肽中的β-发夹结构，而光滑的受限壁则通过形成有序的水层来稳定它，这些水层使十肽在孔的内部保持溶剂化并远离表面。此外，我们表明受限孔的大小可以调节寿命值，其中与十肽大小相当的孔尺寸影响最大。
